TW200410703A - Pharmaceutical composition - Google Patents

Abstract

A pharmaceutical composition, which comprises, as active ingredients, bisacodyl, sennoside or a salt thereof, and a vitamin.

Description

200410703 V. Description of the invention (l)-The technical field to which the invention belongs The present invention relates to a pharmaceutical composition, more chain &-a pharmaceutical composition, which promotes bowel movements and at the same time relates to rough skin. Edema has a therapeutic effect . "Contemporary constipation is a technique that reduces the symptoms of discomfort when the number of bowel movements or the amount of defecation is healthier. In the medicament for the treatment of constipation, the" emergency laxatives "produced by the constipation and the" laxatives "acting on the large intestine Yu] intestinal constipation drugs are mainly used in the latter. "Don't" 2 kinds, but generally used "4 doses to increase the intestinal osmotic pressure to make water," "abdominal expansion" to absorb water and swell in the intestine, For "irritant thirst" that stimulates the intestinal wall, use "irritant laxative" that stimulates the large intestine. Slavery medicine. In the mouth, however, the previously provided laxative sometimes still works and 'constipation and rough skin and edema are considered; two: L Lu boat yarn. Ϊ́ constipation drugs have the "skin and round edema associated with constipation" "Easy performance. However, Xilou # 1 > Constipation relieves and produces vomiting ^ 1 The relieving effect depends only on the improvement of constipation. Therefore, the medicine for constipation cannot be regarded as absolutely satisfactory. SUMMARY OF THE INVENTION ... The medicine for constipation is expected. # e & λ The purpose of the present invention is to provide a constipation medicine, 苴 1 constipation treatment effect, and the treatment effect is also good / combination & constipation caused by rough skin · edema treatment 7042-5704 -PF (Nl) .ptd Page 5 200410703 V. Description of the invention (2) As a result of diligent review by the present inventors and others to solve the above-mentioned problems, it was found that if Bisa, which is currently known as a constipation treatment agent or a defecation promoter, can bite Bisacodyi) and Sennoside have a more effective diarrhea effect than when they are used individually. Furthermore, if vitamins are added to these combinations, they can quickly cause constipation. The effect of the invention is to roughen the skin and relieve edema, and the present invention has been completed. P. The invention provides a medicinal composition comprising bisacodide or its salt and vitamins as active ingredients. In the pharmaceutical composition of Ming, used as an active ingredient, bisacodyl is as follows:

The effect of A, ′ /, directly acts on the intestinal mucosa, and has 45 ′, ′, used as a defecation promoter at first. it Another active ingredient, senna, is as shown in the following formula (2)

200410703

V. Description of the invention (3)

The compound shown also stimulates the large intestine to make the large intestine peristaltic and active, and has the effect of promoting defecation in the natural state, and is a chemical used for the treatment of constipation. Examples of the salt of the senna spine include calcium salts. In the present invention, these two compounds are used in combination for the purpose of constipation treatment, in order to obtain a more effective diarrhea effect which cannot be obtained by using them alone. In order to obtain such an effect, the proportion of each compound is by weight, and 1 part of senna or its salt is in the range of 0.5 to 10, more preferably in the range of 1 to 5. Right skin: Another active ingredient vitamins can be used-general display ί C Λ Λ such as vitamin A, vitamin h, B6, vitamins, dermatitis, and other raw materials, pantothenic acid, etc. Among them, it is preferable to have treatment and so on. χ 人 @ Vitamin 类 ’Specific examples include vitamin β2

1 is preferably in the range of 0.05 to 20, and more preferably 0.1 to 1. 200410703 V. Description of the invention (4) In the case of vitamin Bβ, one portion of sand can be bitten, preferably in the range of 0 · 100 and more preferably in the range of 0.2 · 5. I wish that the pharmaceutical composition of the present invention can be prepared into a desired dosage form by combining the above three ingredients with appropriate additives. People of the medical group of the present invention: Examples of = types include, for example, lozenges (including chewable tablets, foamed tablets), Mu ° people, pills, granules, fine granules, powders, licks, and clever bodies; = 'Well-known formulations suitable for these dosage forms can also be used. Among them, enteric formulations are particularly preferred. βρ, ί ί Ming t pharmaceutical composition specific manufacturing examples are as follows. With the given amount of bisacodyl and glycosides or their salts, it is usually mixed with the required formulation additives to homogeneous Π 2 'and it is based on excipients, binding agents, and disintegration: Additives, for example, electric agent = chemical source: flavor Γ: flavor Γ agent, fluidizer, anti-fragrance agent, fragrance, Guanxiang 桥, bridge flavoring agent, cooling agent, colorant, additive. Fang Xiangjian can generally add preparations for solid preparations to the "human" mixture, and use the granulation method that contains water or the same according to the private use, such as manufacturing. The ritual method is to use granulation method to make granulated powder. It can be used as granules, fine granules or powders. For example, it can be sieved as needed or its size can be adjusted by pulverization and then withered. In addition, if the intended dosage form is a lozenge, 7040 * 57〇4 * PF (Nl) .Ptd page 8 200410703 V. Description of the invention (5) --- The granulated powder obtained in the above manner is then used. After mixing with the formulation additives as required, compression molding is performed by a conventional method, and coating is performed as needed to prepare. Capsules can be produced by filling the granulated powder with capsules using a capsule filling machine. '

The pharmaceutical composition of the present invention produced in the above manner can be effectively used as a laxative for the treatment of constipation. The dosage of the medicinal composition varies depending on the patient's convenience, course, age, etc. For adults, the active ingredient is bisacodyl, about 20 mg per person per day, and senna or its salt is 3 to 3 per day. About 50 mg, the vitamins are preferably 2 to 100 mg per day, and can be administered orally by dividing 3 times a day.

(Effects) In a medicinal pharmaceutical composition, by combining bisacodyl and panfan or a salt thereof, a laxative with a more effective diarrhea effect can be obtained. The reason is that it is related to the pharmacological effect of intestinal mucosa ± ^ Related to the point of action. ^ Produced by the sensation of sweetness, the & system combined with vitamins can quickly relieve the rough skin and edema associated with constipation. The reason is considered to be related to the intestinal vitamins B2, B6 and other intestines. p, κ, · 疋 by intestinal bacteria

(It is produced by BdidobactenunO. During constipation, the push flora loses its balance and makes vitamins deficient. 疋 Because of the intestinal family, on the other hand, it has been reported that human kappa is related to the process of abnormal lipid peroxidation and peroxidation. Opinions that are related to and cause potential life-sustaining 'β, dysfunction> large consumption often lacks β2. Conversely, 200410703, description of the invention (6) increase in lipids (example) Someone ... if vitamins ^ If the vitamins are sufficient, the quality will increase, and the result will improve the skin roughness and edema. The following examples and test examples will be used to explain the present invention in more detail, but the present invention is not due to such implementation. Examples are subject to any limitation. Test Example 1 The combined effect of vegetatives: Using mice as experimental animals, the following test methods were used to explore the therapeutic effect of Vital Be on the symptoms of rough seams. Also, due to ^ It is difficult to induce rough skin accompanied by constipation on animals and there is no uniform test mode 4, so the effect of vitamin & and ββ administration on the dermatitis alone mode is reviewed. Dermatosis The results of macroscopic observations show the grade 々a 丨 丨 丨 1, and the results of the k-histological examination are shown in Table 2. 〈Test method〉 a) Target animal 3-week-old Cr j: CD-1 (ICR) male stingy b) Group composition ① Normal feed-control group ② Vitamin B2 and B6 deficient feed-control group Β; low-dose administration group I, Xichuan no-administration group h high-dose administration group ③ vitamin B2, B (; lack of feed Vitamins & ④ Vitamin dagger and beta β deficiency feeds 太 Vitamin dagger and beta 6 deficiency feeds-vitamin β2 c) Test substance vitamin B2 and vitamin dagger

7042-5704-PF (Nl) .ptd 200410703 V. Description of the invention (7) d) Sodium carboxymethylcellulose, olive e) Method of administration Bar and administered orally once a day for 9 days f) Dermatitis is induced after the test substance is administered s ^ it ^ ^ p ^ ^ ^ ^ ^ into hair removal, and after 7 days, the dandan oil dissolved in olive oil is applied to each part for 20 minutes from summer. g) Observation of the degree of dermatitis (right cochlea and back skin), pathological examination (right cochlea and back skin) h) Observation of dermatitis after 6, 1 2, 2 4, 4 8 hours i) Evaluation criteria (i) Observation of skin symptoms (6, 12, 24, 48 hours after dermatitis induction) The degree of dermatitis of the right ear and back skin was scored with the naked eye according to the following criteria. 〇 (No change) 1 (weak erythema) 2 (moderate erythema) 3 (strong erythema and edema) (ii) Histopathological examination (6, 12, 24, 48 hours after dermatitis induction) Observation by microscopy The degree of neutrophil infiltration, edema, ulcers, and scabs was scored based on the following criteria. 0 (no change) 1 (weak erythema) page 11 7042-5704-PF (Nl) .Ptd 200410703

7042-5704-PF (Nl) .ptd Page 12 200410703 V. Description of the invention (9)

SS 2.3 * ± 0.1 ± 0.2 (η = 12) (η = 12) (η = 12) (η = 12) 0 · 3 0.75 ο ο 04 20 • Qiqian i ± 0.1 S.2 Β2 & Β6 (η = 12 ) (η = 12) (η = 12) (η = 12) 1 2.5 bath ~ pet 0 〇 0.4 1.7 Wei HS ± 0.2 (η = 12) (η = 12) (η = 12) (η = 12) 3 7.5 〇〇0 · 3 1.3 # ± 0.1 ± 0.1 (η = 12) (η = 12) (η = 12) (η = 12) 〇 ο 0CO ± 0.1 (η = 9) 0.6 ± 0.2 (η = 9) ± 0.2 (η = 9) ± 0.2 (η = 9) 11 ± 0.2 (η = 9) 1.9 ± 0.2 (η = 9) 1.6 ± 0.2 (η = 9) 1.4 * ± 0.2 (η = 9) 0.7 ± 0.2 (η = 6) 0.5 ± 0.2 (η = 6) 0.5 ± 0.2 (η = 6) 0.3 ± 0.2 (η = 6) 1.3 ± 0.3 (η = 6) 1.5 ± 0 · 2 (η = 6) 1.3 ± 0.2 (η = 6) 1.3 ± 0.2 (η = 6) (η = 3) (η = 3) 〇 (η = 3) 〇ϊ) 〇 (η = 3) 〇 〇 (η = 3) 〇 (η = 3) Ο (η = 3) Ο

S 妹妹 岭 0 0 0.2-5οσΝ-α \ ε 1.3 Wei ± 0.1 ± 0.2 ± 0.2 scofe ^ sro (n = 10) (η = 3 (η = 3 (η = 3 (η = 3 (n = 3 ( η = 3 (n = 10) (η = 3 (η = ο Tellurium 1-H 銮 1-H-based tellurium 1-H teletellurium 1-¾ £) Lean sour lacquer ¾¾ iB2 Ϊ6 涔 ft (3¾

6tM 24, M2rl 4οο, Μ3τέ _ 4 7042-5704-PF (Nl) .ptd Page 13 200410703 V. Description of the invention αο) From this result, it can be considered that with the increase in the dose of vitamin B2 and vitamin B6, the back skin and the The cochlear erythema score tends to be lower. Histopathological examination:

I

7042.5704-PF (Nl) .ptd Page 14 200410703 V. Description of the invention (11) * p < 0.05: Listening (lacquer 忤 姝 B2 ^ lacquer i i BON eggplant effect two X 5%) $ 4m ^) 3 7.5 1 2.5 s Ho 0.3 Ho 0, -Gongii 10 Β256 ± 0 0.3 0.75 eggplant 4: ¾ 10 Wei ± 0 1.3 ± 0.3 10 Ho 0.7 ± 0.3 1.0 K-0 1.3 Ho. 3 0.7 ± 0.3 10 ± 0.6 0 * Ho 10 ± 1.0 0 Ho 0 Ho 0 Ho 10 Ho 1.0 Ko 10 Ho 0.3 ± 000 10 ss Ho 10 ± 0 1.0 Ho 1.0 Ho 0.7 ± 0.3 0.7 ± p3 0.7 ± 0.3 0.7 ± 0.3 0 Ho 0.3 ± 0.3 1.3 ± 0.3 1.3 ± 0.3 2.0 Ho 0.3 ± 0.3 1.7 Ho. 3 20 ± 0 1.3 ± 0.3 1.3 ± 0.3 0.7 ± 0.3s Ko 0.7 ± 0.7 0.3 ± 0.3 0.7 dbo.3 0 Ho 0.3 ± 0.3 0 Ho 诿阼 幡 ian 3r Wei 6+ 1, 2 · 24+ 48, h 6+ 12 ψ 24+ 400+ 6+ 12+ 24+ 400+ Spider B2 Ling B6 fi fi β β β fi fl β β β 5 ^ ( mg / kg) is # 7042-5704-PF (Nl) .ptd Page 15 200410703

From this result, it is considered that as the doses of vitamin Bz and vitamin Be increase, the infiltration and edema of the back skin and cochlea cells tend to decrease. As shown in the above results, it was confirmed that vitamins & vitamins and vitamin D are effective in improving the skin symptoms of the croton oil dermatitis inducing model of vitamin b2 and vitamin D deficiency mice. Therefore, it is judged that the simultaneous intake of vitamin β2 and vitamin dagger when taking a constipation therapeutic agent is effective for improving skin symptoms. Example 1 (a) Preparation of core spinner According to the composition shown in Table 3 below, a core tablet (bare tablet) of 5 5 mg per tablet was prepared in a pestle with a radius of 5 · 5 mm Φ and 4 · 5_R. The hardness of the tablet was 2.8 kg f, and the disintegration time (test liquid; water) was 6 to 8 minutes. Table 3 Ingredient 1 tablet (mg) Bisacodyl 5.0 senna replacement salt (Sennoside Calcium) 13.3 Vitamin B Beta (pyridoxine_HCl) 5.0 Vitamin B2 (riboflavin) 2.0 Avicel PH-101 5.5 Lactose 22.7 Talc 0.5 Magnesium Stearate 1.0 Total 55.0

7042-5704-PF (Nl) .ptd Page 16 200410703

Put 4.7 kg of β-Hai tablet into a vented pan coating (Hicoater HCT-48; manufactured by Floyd Industrial Co., Ltd.), with air supply temperature of 50 C and product temperature on one side The plasticizer solution of triethyl citrate / glycerol fatty acid (35/20) was sprayed at a spray speed of 20 g / min at 45 ° C and a rotation number of 16 rpm. Cellulose acetate succinate (trade name AS-MF manufactured by Shin-Etsu Chemical Industry Co., Ltd./talc (mixing ratio 丨 〇 / 6)) was uniformly dispersed at 58 g / min to form a dry film to obtain each tablet. 67 Korean enteric film-coated keys; (b) Production of sugar-coated tablets, based on the enteric film-coated tablets manufactured in (a) above, using a ventilated liquid coating film coater (Hicoater HCT-48; Floyd Manufactured by German Industry (Stock) Co., Ltd., using 65% sucrose syrup to form a sucrose layer (film) with a thickness of 5 mg per tablet and a film thickness of 48. Nanling clay 10%, calcium carbonate 10%, talc 5%, titanium oxide A water suspension consisting of 5%, acacia powder 4% and sucrose 40% forms a smooth layer of 35mg per tablet. Finally, 65% sucrose syrup with caramel pigment is added to form 5mg per tablet. Enteric-coated sugar-coated tablets are obtained by coloring the layer and polishing it with wax. (Industrial availability) The pharmaceutical composition of the present invention has a more reliable diarrhea effect than the previous constipation treatment agents such as laxatives. Since the pharmaceutical composition of the present invention is supplemented with vitamins such as vitamins &, & in addition to the previous laxatives, it can quickly relieve skin roughness and edema caused by constipation. Therefore, the pharmaceutical composition of the present invention can be widely used It is used as an agent for constipation that has a therapeutic effect on skin roughness and edema caused by constipation.

200410703

7042.57Q4-PF (Nl) .ptd Page 18

Claims (1)

200410703 VI. Scope of patent application 1. A pharmaceutical composition, which contains Bisacodyl, Fanbin? (Sennoside) or its salts and vitamins as active ingredients. 2. The pharmaceutical composition according to item 1 of the patent application, wherein the vitamins are vitamin B2 and / or vitamin B6. 3 The pharmaceutical composition according to item 1 or item 2 of the patent application scope, which is a laxative. 〇 7042-5704-PF (Nl) .ptd Page 19